POS1240 EFFICACY AND SAFETY OF ABATACEPT IN MYOSITIS ASSOCIATED INTERSTITIAL LUNG DISEASE
Authors: R. Aggarwal, S. Moghadam-Kia, D. Koontz, D. Saygin, S. Bae, D. Sullivan, G. Marder, S. Venuturupalli, P. Dellaripa, S. Danoff, T. Doyle, G. Hunninghake, J. S. Lee, A. Fischer, J. Falk, C. R. Kang, Y. Lin, C. Johnson, D. Ascherman, C. V. Oddis
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Interstitial Lung Disease (ILD) is the most common cause of mortality in myositis and there is lack of randomized clinical trials for myositis-associated ILD (MA-ILD). A T-cell mediated pathogenesis has been postulated for MA-ILD, and abatacept (ABA) is a T cell co-stimulatory modulator. <h3>Objectives</h3> Our primary objective was to evaluate the efficacy, safety and tolerability of ABA (125 mg SQ weekly) combined with standard of care (SOC) vs. placebo/SOC in MA-ILD patients in a multi-center, double-blind, randomized placebo-controlled proof of concept clinical trial. <h3>Methods</h3> 20 patients (pts) with anti-synthetase antibody (Anti-Syn Ab) were enrolled across 5 centers for 24 weeks in a randomized placebo-controlled phase (RCT) followed by an open label extension (OLE) for 24 weeks. Active myositis was not required but pts must have had active ILD (new onset or worsening requiring treatment) and previously failed ≥1 SOC drug for ILD. Pts were required to be on stable SOC [glucocorticoids (GC)/1 immunosuppressive (IS) agent (azathioprine or mycophenolate) prior to the trial as well as stable SOC IS throughout the trial]. A recommended GC taper was instituted. The primary endpoint was the change in Force Vital Capacity (FVC) (in ml) change from baseline to week 24. Secondary endpoints included FVC changes over 48 weeks, patient reported outcomes (PRO) of dyspnea (UCSD-shortness of breath questionnaire; range 0-120, MCID of 8) and DLCO corrected % predicted (DLCO) at 24 and 48 weeks. Mixed effect modeling was used for analysis and the study was not powered for primary or secondary outcomes. <h3>Results</h3> A total of 20 anti-Syn Ab positive pts (mean age of 57, 45% female and 85% Caucasian, Jo-1, 55%) were randomized to ABA (n=9) and placebo (n=11). All but 1 pts completed 48 weeks of the trial. There was no significant or clinically relevant difference in median FVC (ml) from baseline to week 24 between ABA (-40 ml) and placebo (30 ml), p = 0.97. However, the median FVC (ml) change from baseline to week 48 was 140 ml and -40 ml, in ABA vs. placebo (p=0.15), with a 180 ml difference in favor of the ABA group. FVC% predicted remained stable (±5%) or improved (&gt;5%) without death or drug rescue in 75% (6/8) and 45% (5/11) at week 24 and week 48, in ABA vs. placebo, respectively. The median DLCO change from baseline was -4.5 and -10.5 at week 24; 6.5 and -2.7 at week 48, in ABA vs. placebo group, respectively. DLCO remained stable (±5%) or improved (&gt;5%) without death or rescue in 57% (4/7) and 45% (5/11) at week 24; 62.5% (5/8) and 40% (4/10) at week 48, in ABA vs. placebo, respectively. Dyspnea improved by median of 1 and 3 at week 24; 13 and 5 at week 48 in ABA vs. placebo, respectively. Dyspnea improved by an MCID of 8 without requiring drug rescue or death in 22% (2/9) and 45.5% (5/11) at week 24; 50% (4/8) and 18% (2/11) pts at week 48 in ABA vs. placebo, respectively. There were 3 severe adverse events (1 in RCT, 2 in OLE) in 2 pts requiring hospitalization in the ABA group for progressive respiratory failure and 1 died (at 24 weeks). There were 36 and 23 adverse events among 9 placebo and 9 treatment group pts. ABA was well tolerated. <h3>Conclusion</h3> MA-ILD ABA-treated subjects showed similar FVC, DLCO and dyspnea PRO trends compared to placebo at 24 weeks but clinically and numerically meaningful trends were observed in ABA-treated subjects at week 48. These results suggest the need for a larger randomized study of ABA in MA-ILD. Abatacept was relatively safe and well tolerated in the cohort. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> Rohit Aggarwal Consultant of: Mallinckrodt, Octapharma, CSL Behring, Bristol Myers-Squibb, EMD Serono, Q32, Kezar, Pfizer, AstraZeneca, Alexion, Argenx, Boehringer Ingelheim (BI), Corbus, Janssen, Kyverna, Roivant, Merck, Galapagos, Actigraph, Scipher, Horizon Therapeutics, Teva, Beigene, ANI Pharmaceuticals, Biogen, Nuvig, Capella Bioscience, CabalettaBio., Grant/research support from: Mallinckrodt, Pfizer, Bristol Myers-Squibb, Q32, EMD Serono, Janssen, Boehringer Ingelheim (BI) , Siamak Moghadam-Kia: None declared, Diane Koontz: None declared, Didem Saygin: None declared, Sangmee Bae: None declared, Daniel Sullivan Shareholder of: Dr. Sullivan own shares in the following relevant companies: Eli Lilly, Johnson and Johnson, Merck, Amgen, and the CURE ETF (in addition to the above, contains Pfizer, AbbVie, and Abbott Laboratories)., Galina Marder Grant/research support from: Research Grant from GSK, Swamy Venuturupalli Consultant of: Kezar Pharmaceuticals, Grant/research support from: Mallinckrodt Pharmaceuticals and Horizon Pharmaceuticals , Paul Dellaripa Grant/research support from: Yes, from Bristol Myers and Genentech, Sonye Danoff Consultant of: Boehringer Ingelheim, Grant/research support from: Boehringer Ingelheim Clinical trials - Boehringer Ingelheim, BMS, United Therapeutics, Tracy Doyle Consultant of: Dr. Doyle has received consulting fees from Boehringer Ingelheim, Grant/research support from: Dr. Doyle has received grant support from Bristol Myers Squibb and has been a part of a clinical trial funded by Genentech., Gary Hunninghake Consultant of: Boehringer-Ingelheim, Chugai Pharmaceuticals, and the Gerson Lehrman Group, Joyce S. Lee Consultant of: United Therapeutics, Boehringer Ingelheim, Blade, Eleven P15, Grant/research support from: Boehringer Ingelheim, Pliant, Aryeh Fischer Shareholder of: Bristol Myers Squibb, Employee of: Aryeh is a full-time employee of Bristol Myers Squibb, Jeremy Falk: None declared, Chae Ryon Kang: None declared, Yan Lin: None declared, Cheilonda Johnson: None declared, Dana Ascherman Consultant of: PTC Therapeutics, Lundbeck and EMD Serono, Grant/research support from: Mallinckrodt, TEVA, Argenx and Biogen, Chester V Oddis Consultant of: Pfizer, EMD Serono, Grant/research support from: Genentech.